TopicNeuroscience

VTA

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26Total items

24ePosters

1Grant

1Seminar

Latest

GrantNeuroscience

Molecular strategies for resolving differential regulation of dopamine subpopulations

National Institute of Mental Health

Jun 9, 2028

Project Summary/Abstract Dopamine neurons in the ventral tegmental area (VTA) fire action potentials in complex patterns of tonic and phasic activity in response to environmental stimuli and during behavioral tasks. Transcriptomic, anatomical, and functional studies have established that VTA dopamine neurons can be divided into multiple subpopulations with variable gene expression, projection patterns, and response profiles. We recently completed a transcriptomic study that identified genetic markers for three distinct subpopulations of VTA dopamine neurons, and also found evidence for variability in ion channel gene expression between populations that correlated with differences in activity-dependent gene expression. However, much remains unknown regarding how specific genes encoding ion channels, receptors, transcription factors, or other signaling components contribute to the variability in baseline physiological properties observed across the VTA. Here we propose to combine slice electrophysiology recordings of VTA dopamine neurons with post-hoc single-cell sequencing analysis (i.e. patch-seq), which will allow us to directly correlate gene expression and physiological properties in order to identify candidate genes that may be key drivers of the variability between subpopulations. We also propose to validate and utilize a novel dual-recombinase CRISPR/Cas9 system for targeted gene mutagenesis in intersectional neuronal populations, which will provide a mechanism for testing gene function with unprecedented precision. We will use this approach to test the function of two candidate ion channel genes, the potassium channels Kcnh5 and Kcnh7, previously identified in our transcriptomic study as potential contributors to dopamine neuron action potential firing properties. We hypothesize that these genes are important for enabling rapid action potential firing in highly excitable dopamine neurons found in specific subpopulations. As a whole, with this proposal we aim to generate a valuable dataset linking gene expression in VTA dopamine neurons with physiology and subpopulation identification, as well as develop an intersectional gene mutagenesis strategy that can be used throughout the brain to precisely target neuronal subpopulations to test gene function. With this approach, we hope to facilitate future precision targeting of the dopamine system and dopamine-dependent behaviors.

SeminarNeuroscienceRecording

On places and borders in the brain

Dori Derdikman

Technion

May 20, 2021

While various forms of cells have been found in relation to the hippocampus cognitive map and navigation system, how these cells are formed and what is read from them is still a mystery. In the current lecture I will talk about several projects which tackle these issues. First, I will show how the formation of border cells in the coginitive map is related to a coordinate transformation, second I will discuss the interaction between the reward system (VTA) and the hippocampus. Finally I will describe a project using place cells as a proxy for associative memory for assessing deficits in Alzheimer’s disease.

VTA

Latest

Molecular strategies for resolving differential regulation of dopamine subpopulations

On places and borders in the brain

Newly Formed Synapses Between VTA Projections and ACC Pyramidal Neurons in Response to Chronic Social Defeat Stress Differentiate Stress Susceptible From Stress Resilient Mice

VTA dopamine neurons signal phasic and ramping reward prediction error in goal-directed navigation

Chronic nicotine alters motivational value of natural rewards through circuit-based alterations in VTA dopamine neurons

VTA circuitry sustains opposite responses of dopaminergic neurons to drugs of abuse

Contribution of GirK channels expressed in VTA GABAergic neurons to anxiety, social behaviors and hippocampal-dependent memory

VTA dopamine neurons orthogonally encode motivated behaviours

Effects of VTA activation on the recovery process following myocardial infarction

Locomotor control by theta-range activation of glutamatergic MSDB to VTA projections

Neural signaling in the VTA-accumbens axis correlated with cannabis extract effects on methamphetamine conditioned place preference in mice

Nicotinic receptors promote susceptibility to social stress in female mice linked with neuroadaptations within VTA dopamine neurons

Postnatal IL-4 administration induces long-term dysfunction in cerebellar-VTA connectivity

Progressive hyperpolarization-activated cation current (Ih) reduction: a response mechanism to decrease cocaine-induced excitability in VTA DA neurons

The survival of VTA dopamine neurons is associated with upregulation of Ca2+ binding proteins in the Tg2576 model of Alzheimer’s Disease

Vicarious reward signals in the VTA drive prosocial choices in rats

Anatomofunctional characterization of the tail of the ventral tegmental area (tVTA/RMTg) in mice

VTA circuitry sustains opposite responses of dopaminergic neurons to drugs of abuse

Dissecting the effects of distinct VTA projections on peripheral immunity

Dynamic dynorphin release in the VTA during appetitive and aversive associative learning

Glutamatergic and GABAergic mu-opioid receptor VTA neurons differentially modulate motivational and somatic consequences of fentanyl use

Mapping the neural circuitry: LC-NE neurons and their connections to VTA and Raphe nuclei

Maternal Fmr1 deficiency dysregulates offspring sociability and oxytocinergic signaling in the VTA

Opposite coding of competing rewards by VTA dopamine neurons

Stimuli-evoked noradrenergic activity in the VTA drives phasic dopamine release in the nucleus accumbens – preliminary results

Worry not, the VTA has the BNST under control… or does it?